دورية أكاديمية
Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.
| العنوان: | Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase. |
|---|---|
| المؤلفون: | Rawat C; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Ben-Salem S; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Singh N; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Chauhan G; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Rabljenovic A; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Vaghela V; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Venkadakrishnan VB; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio.; Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio., Macdonald JD; Center for Therapeutics Discovery, Cleveland Clinic, Cleveland, Ohio., Dahiya UR; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Ghanem Y; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Bachour S; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, Ohio., Su Y; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., DePriest AD; Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Lee S; Department of Urology, UC San Diego, La Jolla, California., Muldong M; Department of Urology, UC San Diego, La Jolla, California., Kim HT; Department of Urology, UC San Diego, La Jolla, California.; Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Kumari S; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Valenzuela MM; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio., Zhang D; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.; School of Biomedical Sciences, Hunan University, Changsa, China., Hu Q; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Cortes Gomez E; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Dehm SM; Masonic Cancer Center and Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, Minnesota., Zoubeidi A; Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Canada., Jamieson CAM; Department of Urology, UC San Diego, La Jolla, California., Nicolas M; Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio., McKenney J; Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio., Willard B; Proteomics Core Facility, Cleveland Clinic, Cleveland, Ohio., Klein EA; Department of Urology, Cleveland Clinic, Cleveland, Ohio., Magi-Galluzzi C; Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio., Stauffer SR; Center for Therapeutics Discovery, Cleveland Clinic, Cleveland, Ohio., Liu S; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Heemers HV; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio. |
| المصدر: | Cancer research [Cancer Res] 2023 Dec 15; Vol. 83 (24), pp. 4142-4160. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Prostate*/pathology , Prostatic Neoplasms*/drug therapy , Prostatic Neoplasms*/genetics , Prostatic Neoplasms*/metabolism , Protein Kinases*/metabolism, Humans ; Male ; Cell Line, Tumor ; Cell Proliferation ; Signal Transduction |
| مستخلص: | Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2-Skp2-p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression. Significance: The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression. See related commentary by Mishra et al., p. 4008. (©2023 American Association for Cancer Research.) |
| التعليقات: | Comment in: Cancer Res. 2023 Dec 15;83(24):4008-4009. doi: 10.1158/0008-5472.CAN-23-2858. (PMID: 38098450) |
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| معلومات مُعتمدة: | U24 CA274159 United States CA NCI NIH HHS; U24 CA232979 United States CA NCI NIH HHS; R01 CA174777 United States CA NCI NIH HHS; R01 CA166440 United States CA NCI NIH HHS; S10 OD023436 United States OD NIH HHS; R01 CA248048 United States CA NCI NIH HHS |
| المشرفين على المادة: | EC 2.7.- (Protein Kinases) EC 2.7.1.- (citron-kinase) VY778IXU5T (OTS167) |
| تواريخ الأحداث: | Date Created: 20231006 Date Completed: 20231220 Latest Revision: 20240616 |
| رمز التحديث: | 20240616 |
| مُعرف محوري في PubMed: | PMC10841833 |
| DOI: | 10.1158/0008-5472.CAN-23-0883 |
| PMID: | 37801613 |
| قاعدة البيانات: | MEDLINE |
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